LA JOLLA, Calif.—T cell exhaustion is a phenomenon that occurs when the body dampens the immune system in the face of
a virus or tumor (such as HIV infection) has taken hold and overwhelmed it. Normally in the face of a health invader, the immune system floods the problem
areas with T cells, or T lymphocytes, white blood cells that can help fend off infected or damaged cells. The reason the body can put on the breaks and halt
an immune response, as noted by TSRI Professor Linda Sherman, is that “T lymphocytes are very destructive, so if the virus is there to stay, the body
wants the immune system to shut off to stop doing damage to the organism.”

Sherman was senior author of a new study
examining this phenomenon and the protein responsible for hampering the immune system. The study, “PTPN22 contributes to exhaustion of T cell
lymphocytes during chronic viral infection,” appeared in Proceedings of the National Academy of Sciences.

The protein in question is PTPN22 (protein tyrosine phosphatase nonreceptor type 22 gene), which is expressed in all immune cells. As noted in the
paper, PTPN22 is responsible for “suppression of T cell receptor signaling and promoting efficient production of type I interferons (IFN-I) by myeloid
cells.”

Individuals who have an altered form of this protein have a significantly increased risk for type 1
diabetes and other autoimmune diseases; the Genetics Home Reference of the U.S. National Library of Medicine cites rheumatoid arthritis, systemic lupus
erythematosus and Graves disease as conditions that arise from abnormal copies of this gene and its protein.

Given
how PTPN22 affects the immune system, Sherman and her colleagues wondered if a lack of the protein could consequently prevent the immune system from
triggering T cell exhaustion. They sought to answer that question using mouse models infected with a clone of lymphocytic choriomeningitis virus (LCMV),
which results in chronic infections similar to HIV and hepatitis. Mice without PTPN22 were able to clear the LCMV infections, but mice with PTPN22 presented
with chronic infection and signs of T cell exhaustion.

“The animals deficient in the PTPN22 protein shrugged
off the virus very quickly, rather than having the immune system shut down the way it normally does when it encounters this virus,” added
Sherman.

Moving forward, the team
plans to study PTPN22's role in other cells as well, with Sherman noting that “We have to understand what’s going on so we can take advantage
of that to make new types of drugs.”

Other authors of this study included Christian J. Maine, John R.
Teijaro and Kristi Marquardt, all of TSRI at the time of the study.